title: A mathematical model of the initial interaction between Mycobacterium tuberculosis and macrophages.
abstract: There is a large body of literature describing molecular level interactions between Mycobacterium tuberculosis (Mtb) and macrophages. Macrophages initiate a range of anti-bacterial mechanisms in response to infection, and Mtb is capable of surviving and circumventing many of these responses. We apply a computational approach to ask: what are the effects on the cellular level of these opposing interactions? The model considers the interplay between bacterial killing and the pathogen's interference with macrophage function. The results reveal an oscillating balance between host and pathogen, but the balance is transient and varies in length, indicating that stochasticity in the bacterial population or host response could contribute to the diverse incubation periods observed in exposed individuals. The model captures host and strain variation and gives new insight into host-pathogen compatibility and co-evolution.
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden. Electronic address: epienaar@umich.edu.
authors.forename: Elsje
authors.initials: E
authors.lastname: Pienaar
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Lerm
mesh_terms: D015169:Colony Count, Microbial; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007109:Immunity; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D050296:Microbial Viability; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology; D014774:Virulence
keywords: 6kDa early secreted antigenic target.; ESAT-6; IFN-γ release assay; IGRA; Individual-based model; Macrophage function; Mtb; Mycobacterium tuberculosis; RNS; ROS; TB; TST; Tuberculosis; Variable disease outcomes; reactive nitrogen species; reactive oxygen species; tuberculin skin test